DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This Application filed on 01/03/2025 is a continuation of 18/648,049 filed on 04/26/2024 which is a 17/449,785 filed on 10/01/2021 which is a continuation of PAT 11135214 filed on 05/13/2019 , which has a PRO 62/670,253 filed on 05/11/2018.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 5/27/25(2) is in compliance with the provisions of S7 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
The following rejections are made:
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 117-118, 121-134 and 136 are rejected under 35 U.S.C. 103 as being unpatentable over Vernier et al. ( US20110003850 A1) in view of CDER (Food-Effect Bioavailability and Fed Bioequivalence Studies. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2002).
Vernier et al. teaches a method of treating or preventing a disease, disorder, or condition that is affected by modulation of at least one potassium ion channel selected from KCNQ2/3, KCNQ4, and KCNQ5, such as treating or preventing a seizure disorder in a patient comprising administering compound A:
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in an amount of from about 10 mg to about 2000 mg per day to a patient. [0337] Tests examples show oral administration of the compound. [0529]
While, Vernier et al. does not specify treatment under fed conditions,
CDER teaches food-effect bioavailability (BA) “studies may be exploratory and descriptive, or a sponsor may want to use a food effect BA study to make a label claim. The following exposure measures and pharmacokinetic parameters should be obtained from the resulting concentration-time curves for the test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life • Other relevant pharmacokinetic parameters. Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended for food-effect BA (to make a claim of no food effects) and fed BE studies, analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax ) prior to analysis is recommended. The 90 percent CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-t, and Cmax.” “For IND or NDA food-effect BA studies, the fasted treatment serves as the reference. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment. The effect of food on the absorption and BA of a drug product should be described in the CLINICAL PHARMACOLOGY section of the labeling. In addition, the DOSAGE AND ADMINISTRATION section of the labeling should provide instructions for drug administration in relation to food based on clinical relevance (i.e., whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food).”
It would have been obvious to one of ordinary skill in the art at the time of filing to test a human subject under fasted or fed conditions. The motivation to test a human subject under fasted or fed conditions is because CDER teaches to test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life in order to see whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions. It would have been obvious to one having ordinary skill in the art at the time the invention was filed to modify the time and meal-type, since it has been held that consumption with food results in different safety or efficacy, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food, discovering the optimum time and meal-type involves only routine skill in the art.
Claims 118 and 135 are rejected under 35 U.S.C. 103 as being unpatentable over Vernier et al. ( US20110003850 A1) and CDER (Food-Effect Bioavailability and Fed Bioequivalence Studies. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2002), as applied to claims 117-118, 121-134 and 136 above in view Johannessen et al. (Management of Focal-Onset Seizures. Qrugs, 2006, Volume 66, Number 13, Page 1704}.
Vernier et al. and CEDR et al. fail to specify seizure focal onset.
Johannessen et al. teaches focal onset seizures are manifestations of abnormal epileptic firing of brain cells in a localized area or areas of the brain.
It would have been obvious to one of ordinary skill in the art at the time of the invention to treat focal onset seizures. The motivation comes from the general teaching that compound A is useful in treatment of seizure disorders. Hence, a skilled artisan would have reasonable expectation of successfully achieving similar efficacy and results.
Claims 119 and 120 are rejected under 35 U.S.C. 103 as being unpatentable over Vernier et al. ( US20110003850 A1) and CDER (Food-Effect Bioavailability and Fed Bioequivalence Studies. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2002), as applied to claims 117-118, 121-134 and 136 above in view Cooper et al. (Repetitive transcranial magnetic stimulation for the treatment of drug-resistant epilepsy: A systematic review and individual participant data meta-analysis of real-world evidence. Epilepsia Open. 2017 Dec 27;3(1):55-65. doi: 10.1002/epi4.12092).
Vernier et al. and CEDR et al. fail to specify increasing RMT or AMT and decreasing corticospinal or cortical excitability.
Cooper et al. relates treatments of seizures with increases RMT or AMT and decreasing corticospinal or cortical excitability.
It would have been obvious to one of ordinary skill in the art at the time of the invention to treat seizures by increasing RMT or AMT and decreasing corticospinal or cortical excitability. The motivation comes from the general teaching that treatments of seizures is associated with increase in RMT or AMT and decrease corticospinal or cortical excitability. Hence, a skilled artisan would have reasonable expectation of successfully achieving similar efficacy and results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117, 124-135, and 143-146 of U.S. Applic. No. 18679045 in view of CDER (Food-Effect Bioavailability and Fed Bioequivalence Studies. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) December 2002). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of administering Compound A to a human in need thereof; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6-dimethylpheny1]-3,3- dimethylbutanamide; the improvement comprising administering Compound A to the human without dose titration while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
While the claims do not specify treatment under fed conditions.
CDER teaches food-effect bioavailability (BA) “studies may be exploratory and descriptive, or a sponsor may want to use a food effect BA study to make a label claim. The following exposure measures and pharmacokinetic parameters should be obtained from the resulting concentration-time curves for the test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life • Other relevant pharmacokinetic parameters. Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended for food-effect BA (to make a claim of no food effects) and fed BE studies, analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax ) prior to analysis is recommended. The 90 percent CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-t, and Cmax.” “For IND or NDA food-effect BA studies, the fasted treatment serves as the reference. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment. The effect of food on the absorption and BA of a drug product should be described in the CLINICAL PHARMACOLOGY section of the labeling. In addition, the DOSAGE AND ADMINISTRATION section of the labeling should provide instructions for drug administration in relation to food based on clinical relevance (i.e., whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food).”
It would have been obvious to one of ordinary skill in the art at the time of filing to test a human subject under fasted or fed conditions. The motivation to test a human subject under fasted or fed conditions is because CDER teaches to test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life in order to see whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. 12178811. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of treating a depressive disorder in a human in need thereof, comprising administering a therapeutically effective amount of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2.6- dimethylphenyl]-3,3-dimethylbutanamide; wherein Compound A is orally administered to the human under fed conditions while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-21, 24, 35 of U.S. Applic. No. 18921788 – claims filed on 2/28/25; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of enhancing the opening of a Kv7 potassium channel in a human, comprising administering an effective amount of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide; and wherein the human is suffering from anhedonia while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
While the claims do not specify treatment under fed conditions.
CDER teaches food-effect bioavailability (BA) “studies may be exploratory and descriptive, or a sponsor may want to use a food effect BA study to make a label claim. The following exposure measures and pharmacokinetic parameters should be obtained from the resulting concentration-time curves for the test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life • Other relevant pharmacokinetic parameters. Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended for food-effect BA (to make a claim of no food effects) and fed BE studies, analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax ) prior to analysis is recommended. The 90 percent CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-t, and Cmax.” “For IND or NDA food-effect BA studies, the fasted treatment serves as the reference. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment. The effect of food on the absorption and BA of a drug product should be described in the CLINICAL PHARMACOLOGY section of the labeling. In addition, the DOSAGE AND ADMINISTRATION section of the labeling should provide instructions for drug administration in relation to food based on clinical relevance (i.e., whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food).”
It would have been obvious to one of ordinary skill in the art at the time of filing to test a human subject under fasted or fed conditions. The motivation to test a human subject under fasted or fed conditions is because CDER teaches to test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life in order to see whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Applic. No. 18958937– claims filed on 11/25/24; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of treating one or more somatic symptoms of a depressive disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of azetukalneror a pharmaceutically acceptable salt thereof while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
While the claims do not specify treatment under fed conditions.
CDER teaches food-effect bioavailability (BA) “studies may be exploratory and descriptive, or a sponsor may want to use a food effect BA study to make a label claim. The following exposure measures and pharmacokinetic parameters should be obtained from the resulting concentration-time curves for the test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life • Other relevant pharmacokinetic parameters. Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended for food-effect BA (to make a claim of no food effects) and fed BE studies, analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax ) prior to analysis is recommended. The 90 percent CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-t, and Cmax.” “For IND or NDA food-effect BA studies, the fasted treatment serves as the reference. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment. The effect of food on the absorption and BA of a drug product should be described in the CLINICAL PHARMACOLOGY section of the labeling. In addition, the DOSAGE AND ADMINISTRATION section of the labeling should provide instructions for drug administration in relation to food based on clinical relevance (i.e., whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food).”
It would have been obvious to one of ordinary skill in the art at the time of filing to test a human subject under fasted or fed conditions. The motivation to test a human subject under fasted or fed conditions is because CDER teaches to test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life in order to see whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117, 119-123, 126-136, 139-144 and 145-151 of U.S. Applic. No. 18648049– claims filed on 1/3/25; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to method of orally administering Compound A to a human in need thereof, wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide; the improvement comprising orally administering an amount of Compound A to the human under fed conditions while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
While the claims do not specify treatment under fed conditions.
CDER teaches food-effect bioavailability (BA) “studies may be exploratory and descriptive, or a sponsor may want to use a food effect BA study to make a label claim. The following exposure measures and pharmacokinetic parameters should be obtained from the resulting concentration-time curves for the test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life • Other relevant pharmacokinetic parameters. Individual subject measurements, as well as summary statistics (e.g., group averages, standard deviations, coefficients of variation) should be reported. An equivalence approach is recommended for food-effect BA (to make a claim of no food effects) and fed BE studies, analyzing data using an average criterion. Log-transformation of exposure measurements (AUC and Cmax ) prior to analysis is recommended. The 90 percent CI for the ratio of population geometric means between test and reference products should be provided for AUC0-inf, AUC0-t, and Cmax.” “For IND or NDA food-effect BA studies, the fasted treatment serves as the reference. For ANDA fed BE studies, the RLD administered under fed condition serves as the reference treatment. The effect of food on the absorption and BA of a drug product should be described in the CLINICAL PHARMACOLOGY section of the labeling. In addition, the DOSAGE AND ADMINISTRATION section of the labeling should provide instructions for drug administration in relation to food based on clinical relevance (i.e., whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food).”
It would have been obvious to one of ordinary skill in the art at the time of filing to test a human subject under fasted or fed conditions. The motivation to test a human subject under fasted or fed conditions is because CDER teaches to test and reference products in food-effect BA and fed BE studies: • Total exposure, or area under the concentration-time curve (AUC0-inf, AUC0-t) • Peak exposure (Cmax) • Time to peak exposure (Tmax) • Lag-time (tlag) for modified-release products, if present • Terminal elimination half-life in order to see whether or not the changes in systemic exposure caused by co-administration with food results in safety or efficacy concerns, or when there is no important change in systemic exposure but there is a possibility that the drug substance causes GI irritation when taken without food. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19-34 of U.S. PAT. No. 11957675. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a Method of treating anhedonia, comprising administering a therapeutically effective amount of Compound A to a human in need thereof; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide, wherein Compound A is orally administered to the human from between about 30 minutes before to about 2 hours after eating a meal and Compound A is administered at a dose of 5-150 mg per day to the human , while the claims herein are drawn to in a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide.
Furthermore, Applicant claims compound A administered under fed conditions. The Examiner points out a drug is administered to a human subject under fasted or fed conditions. The subject cannot be under any other state, in terms of feeding conditions.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11135214. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patented claims are drawn to a method of orally administering Compound A to a human in need thereof, wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H- isoquinolin-2-yl)-2,6-dimethylphenyl]-3 ,3-dimethyloutanamide; wherein the improvement comprises orally administering an amount of Compound A to the human from between 30 minutes prior to consuming food until 2 hours after consuming food while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide. The specification herein describes “under fed conditions’ refers to the condition of having consumed food during the time period between from about 4 hours prior to the oral administration of an effective amount (e.g., within the therapeutically effective dose range) of Compound A to about 4 hours after the administration of Compound A while the prior art claims between 30 minutes prior to consuming food until 2 hours after consuming food. The claims are rendered obvious.
Claims 117-136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-22 of U.S. Patent No. 11091441B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patented claims are drawn to method of preparing the pharmaceutical composition of claim 7, the method comprising combining the crystalline form of Compound A with the pharmaceutical excipient, carrier, and/or diluent to form the pharmaceutical composition wherein the crystalline form is administered to the human from between 30 minutes before to 2 hours after eating a meal while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide. The difference being the specific hours of the fed state. The specification herein describes “under fed conditions’ refers to the condition of having consumed food during the time period between from about 4 hours prior to the oral administration of an effective amount (e.g., within the therapeutically effective dose range) of Compound A to about 4 hours after the administration of Compound A while the prior art between 30 minutes before to 2 hours after eating a meal. The claims are rendered obvious.
Conclusion
No claims are allowed.
Correspondence
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